- Rational design and screening study of novel lead compound based on acetohydroxyacid synthase structure
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Acetohydroxyacid synthase (AHAS) is a key target and has extensive application in the process of herbicide discovery. However, the problem of weed resistance is gradually serious with long-term excessive use of commercial AHAS-inhibiting herbicides, and so, it is urgent to develop novel herbicides. In this study, a virtual screening was performed based on the active site of AHAS. Then, the hit-10 compound with the IC50 value of 47.41 mg/L was selected as lead compound based on the biological testing. Subsequently, the optimization design and syntheses of lead compound were carried out according to the analyzing results of mechanism and receptor-/ligand-binding mode. Three novel 5-substituted benzyl-1,3,4-thiadiazol-2-carbamic acid phenyl ester derivatives were designed and synthesized. Bioactive assay results of the three target compounds showed that all of them displayed the higher inhibition than lead compound to AHAS, with the IC50 values in the 23.54-32.05 mg/L range, and the inhibition rates were increased by 30-50%. Finally, we also analyzed the possible inhibitory mechanism of the three target compounds based on the molecular docking between AHAS and target compounds. This study would provide a novel chemical structure for the discovery of novel AHAS herbicides. Lead compound with IC50 value of 47.41 mg/L was screened out based on AHAS target. Optimization and syntheses of lead compound were performed, and the inhibition rates of the synthesized compound increased by 30-50%. The possible inhibitory mechanisms were analyzed by molecular docking.
- Jin, Jingnan,Qi, Xiaojuan,Yao, Dandan,Mao, Bangqiang,Li, Jianhong,Zhang, Qingye,Chen, Changshui
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Read Online
- Synthesis, structure determination, and biological evaluation of phenylsulfonyl hydrazide derivatives as potential anti-inflammatory agents
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In our previous research, a novel series of phenylsulfonyl hydrazide derivatives were found to reduce LPS-induced PGE2levels in RAW 264.7 macrophage cells via an inhibition of mPGES-1 enzyme. Recently, it was found that a regioisomeric mixture of phenylsulfonyl hydrazide was formed depending on the reaction conditions, which favor either of two regioisomers. One regioisomer corresponds to a kinetic product (7a–7c) and the other regioisomer corresponds to a thermodynamic product (8a–8c). Among them, the structure of kinetic product 7b was confirmed by measuring single X-ray crystallography. In vitro PGE2assay studies showed that the kinetic product (7a and 7b; IC50= 0.69 and 0.55 μM against PGE2) is generally more potent than the thermodynamic product (8a and 8b; IC50= >10 and 0.79 μM against PGE2). A molecular docking study also exhibited that the kinetic product (7a) has a higher MolDock Score (?147.4) than that of 8a (?142.4), which is consistent with the PGE2assay results. A new potent phenylsulfonyl hydrazide (7d; IC50= 0.06 μM against PGE2) without affecting COX-1 and COX-2 enzyme activities was identified based on these overall results.
- Park, Eun Beul,Kim, Kwang Jong,Jeong, Hui Rak,Lee, Jae Kyun,Kim, Hyoung Ja,Lee, Hwi Ho,Lim, Ji Woong,Shin, Ji-Sun,Koeberle, Andreas,Werz, Oliver,Lee, Kyung-Tae,Lee, Jae Yeol
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Read Online
- Synthesis of N-trifluoromethyl amides from carboxylic acids
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Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.
- Flavell, Robert R.,Liu, Jianbo,Parker, Matthew F. L.,Toste, F. Dean,Wang, Sinan,Wilson, David M.
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supporting information
p. 2245 - 2255
(2021/08/12)
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- Versatile Cp*Co(III)(LX) Catalyst System for Selective Intramolecular C-H Amidation Reactions
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Herein, we report the development of a tailored cobalt catalyst system of Cp*Co(III)(LX) toward intramolecular C-H nitrene insertion of azidoformates to afford cyclic carbamates. The cobalt complexes were easy to prepare and bench-stable, thus offering a convenient reaction protocol. The catalytic reactivity was significantly improved by the electronic tuning of the bidentate LX ligands, and the observed regioselectivity was rationalized by the conformational analysis and DFT calculations of the transition states. The superior performance of the newly developed cobalt catalyst system could be broadly applied to both C(sp2)-H and C(sp3)-H carbamation reactions under mild conditions.
- Chang, Sukbok,Jung, Hoimin,Kim, Dongwook,Lee, Jeonghyo,Lee, Jia,Park, Juhyeon
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supporting information
p. 12324 - 12332
(2020/08/06)
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- Synthetic approaches to a challenging and unusual structure—an amino-pyrrolidine guanine core
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The synthesis of an unreported 2-aminopyrrolidine-1-carboxamidine unit is here described for the first time. This unusual and promising structure was attained through the oxidative decarboxylation of amino acids using the pair of reagents, silver(I)/peroxydisulfate (Ag(I)/S2O82?) followed by intermolecular (in the case of L-proline derivative) and intramolecular trapping (in the case of acyl L-arginine) by N-nucleophiles. The L-proline approach has a broader scope for the synthesis of 2-aminopyrrolidine-1-carboxamidine derivatives, whereas the intramolecular cyclization afforded by the L-acylarginines, when applied, results in higher yields. The former allowed the first synthesis of cernumidine, a natural alkaloid isolated in 2011 from Solanum cernuum Vell, as its racemic form.
- Rippel, Rafael,Pinheiro, Luís,Lopes, Mónica,Louren?o, Ana,Ferreira, Luísa M.,Branco, Paula S.
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- PROCESS FOR PRODUCING CHLOROFORMATE COMPOUND
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The present invention provides a method for safely producing a large amount of chloroformate compound with high yield. The chloroformate compound can be produced by mixing and reacting a solution of triphosgene, an amine and an alcohol compound in a flow reactor. The chloroformate compound can also be produced by mixing and reacting a solution of triphosgene with a solution comprising an amine and an alcohol compound in a flow reactor. The amine is preferably tributylamine, and preferably used in an amount of 0.8 to 3 equivalents relative to an amount of the alcohol compound.
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Paragraph 0079; 0087
(2019/06/20)
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- Discovery of (3-Benzyl-5-hydroxyphenyl)carbamates as new antitubercular agents with potent in vitro and in vivo efficacy
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A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625-6.25 μg/mL). The privileged compounds 3i and 3l showed moderate cytotoxicity against cell line A549. Compound 3l also exhibited potent in vivo inhibitory activity on a mouse infection model via the oral administration. The results demonstrated 3-hydroxyphenylcarbamates as a class of new antitubercular agents with good potential.
- Cheng, Ya-Juan,Liu, Zhi-Yong,Liang, Hua-Ju,Fang, Cui-Ting,Zhang, Niu-Niu,Zhang, Tian-Yu,Yan, Ming
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- Visible-Light-Induced Intramolecular C(sp2)-H Amination and Aziridination of Azidoformates via a Triplet Nitrene Pathway
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Catalytic intramolecular C-H amination and aziridination reactions of o-allylphenyl azidoformates have been achieved under visible-light irradiation, providing a mild, clean, and efficient method for the synthesis of useful benzoxazolones and [5.1.0] bicyclic aziridines. Mechanistic studies suggest that a triplet nitrene acts as the reactive intermediate. The chemoselectivity of the reaction, with alkyl olefin aziridination ? electron deficient olefin aziridination ≈ C(sp2)-H amination ? C(sp3)-H amination was observed, which may be instructive in the development of an understanding of visible-light-induced triplet nitrene transformation reactions.
- Zhang, Yipin,Dong, Xunqing,Wu, Yanan,Li, Guigen,Lu, Hongjian
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supporting information
p. 4838 - 4842
(2018/08/24)
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- Bis-Acetyl Carbazole: A Photoremovable Protecting Group for Sequential Release of Two Different Functional Groups and Its Application in Therapeutic Release
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In this paper, we present fluorescent photoremovable protecting groups (FPRPG) based on bis-acetyl carbazole for the release of two different functional groups such as carboxylic acids, alcohols, thiols, and amines in a sequential fashion. Dual-arm caged bis-acetyl carbazoles with different combinations of two unlike functional groups were synthesized. Photophysical studies showed that caged bis-acetyl carbazoles are blue fluorescent and their emission properties are sensitive to the environment. Sequential photorelease of two different functional groups by bis-acetyl carbazole was analyzed by HPLC, UV and emission spectroscopy. The mechanism of the dual release by bis-acetyl carbazole was investigated and supported by TD-DFT calculations. To demonstrate the applicability of the dual release ability of bis-acetyl carbazole FPRPG, we synthesized a drug delivery system (DDS) in which one arm of bis-acetyl carbazole is linked to the carboxylic functional group of chlorambucil (CBL) and the other arm is attached to the hydroxyl group of ferulic acid ethyl ester (FAEE). In vitro studies showed that our DDS presents excellent properties such as photoregulated dual drug delivery, cellular uptake, and biocompatibility.
- Venkatesh, Yarra,Nandi, Surajit,Shee, Maniklal,Saha, Biswajit,Anoop, Anakuthil,Pradeep Singh
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p. 6121 - 6130
(2017/11/15)
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- The invention relates to a chloroformate ester of the phenol as a raw material of the synthetic method (by machine translation)
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The invention provides a phenol as a raw material for synthesis of phenyl chloroformate, the process comprises the following steps: firstly the 94 kg of phenol is processed into a molten state spare; secondly the above-mentioned phenol transfer to the phenol in the adds by drops the pot, will be transferring the catalyst to the catalyst spray tank; once again the reaction tank is reduced to lower the temperature of the 0 °C, then to the lower part of the reaction tank by adding triphosgene; finally the above reaction tank adopts the nitrogen after catches up with was mad, reduced pressure distillation leaves the chlorine formic acid ester; the invention can avoid the generation of by-products of the diphenyl carbonate, and avoids the generation of waste water, in order to further enhance the purity of the product phenyl chloroformate. (by machine translation)
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Paragraph 0040; 0041; 0042; 0043; 0044
(2017/01/19)
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- Simple and efficient production method for phenyl chloroformate
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The invention provides a simple and efficient production method for phenyl chloroformate. The production method comprises the following steps that firstly, phenol is treated into a molten state for use; secondly, phenol is transferred into a phenol spray tank, and a catalyst is transferred into a catalyst spray tank; thirdly, a circulating refrigerating machine is started, then a temperature control pipeline is controlled, a reaction tank is heated, phosgene is introduced into the reaction tank continuously, then the phenol spray tank is started, stirring is started, the catalyst spray tank is started, and central control samples are taken; finally, gas dispelling is carried out on the reaction tank with nitrogen, and phenyl chloroformate is obtained through reduced pressure distillation. Compared with an existing production technology, by means of the simple and efficient production method for phenyl chloroformate, the reaction time is shortened, and the purity and the reaction efficiency are improved.
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Paragraph 0021-0031; 0035; 0046; 0057; 0065
(2018/02/03)
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- Synthetic method for preparing pure phenyl chloroformate with two-step method
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The invention provides a synthetic method for preparing pure phenyl chloroformate with a two-step method. The method comprises main steps as follows: (1) phenol in a molten state and a small quantity of a catalyst DMF (dimethyl formamide) are added to a flask, stirring is started, phosgene is introduced at a certain temperature, activated carbon is added after complete reaction, nitrogen is introduced to a reaction solution, and crude phenyl chloroformate is obtained after the reaction ends; (2) obtained crude phenyl chloroformate is subjected to reduced pressure distillation, and pure phenyl chloroformate is obtained. Compared with the prior art, the method has the advantages as follows: aftertreatment is simple, use of large quantities of acid-binding agents and solvents is effectively avoided, no industrial waste water is produced, the cost is relatively low, the method is suitable for industrial production, and meanwhile, possible harm to the phosgene can be reduced through improvement of equipment.
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Paragraph 0015-0019; 0022-0024
(2018/02/04)
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- Evaluation of the analgesic effect of 4-anilidopiperidine scaffold containing ureas and carbamates
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Fentanyl is a powerful opiate analgesic typically used for the treatment of severe and chronic pain, but its prescription is strongly limited by the well-documented side-effects. Different approaches have been applied to develop strong analgesic drugs with reduced pharmacologic side-effects. One of the most promising is the design of multitarget drugs. In this paper we report the synthesis, characterization and biological evaluation of twelve new 4-anilidopiperidine (fentanyl analogues). In vivo hot-Plate test, shows a moderate antinociceptive activity for compounds OMDM585 and OMDM586, despite the weak binding affinity on both μ and δ-opioid receptors. A strong inverse agonist activity in the GTP-binding assay was revealed suggesting the involvement of alternative systems in the brain. Fatty acid amide hydrolase inhibition was evaluated, together with binding assays of cannabinoid receptors. We can conclude that compounds OMDM585 and 586 are capable to elicit antinociception due to their multitarget activity on different systems involved in pain modulation.
- Monti, Ludovica,Stefanucci, Azzurra,Pieretti, Stefano,Marzoli, Francesca,Fidanza, Lorenzo,Mollica, Adriano,Mirzaie, Sako,Carradori, Simone,De Petrocellis, Luciano,Schiano Moriello, Aniello,Benyhe, Sándor,Zádor, Ferenc,Sz?cs, Edina,?tv?s, Ferenc,Erdei, Anna I.,Samavati, Reza,Dvorácskó, Szabolcs,T?mb?ly, Csaba,Novellino, Ettore
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p. 1638 - 1647
(2016/10/09)
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- Phenyl chloroformate production technique
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The invention provides a phenyl chloroformate production technique. The technique comprises the steps of firstly, slowly increasing the temperature of a stirring tank, then introducing phosgene constantly into the stirring tank from the middle of the side wall of the stirring tank, opening a phenol dropwise adding tank, and opening the stirring tank and a catalyst spray tank at the same time; secondly, continuing to introduce phosgene, and taking a central control sample; thirdly, continuously extracting the central control sample every other 30 min; fourthly, conducting air expelling with nitrogen on the stirring tank after final sampling is stopped; finally, conducting reduced pressure distillation on materials left after air expelling to obtain phenyl chloroformate. Compared with the prior art, the production technique has the advantages that reaction time is shortened, and purity and reaction efficiency are improved.
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Paragraph 0021-0065
(2018/02/04)
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- In vitro radical scavenging and cytotoxic activities of novel hybrid selenocarbamates
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Novel selenocyanate and diselenide derivatives containing a carbamate moiety were synthesised and evaluated in vitro to determine their cytotoxic and radical scavenging properties. Cytotoxic activity was tested against a panel of human cell lines including CCRF-CEM (lymphoblastic leukaemia), HT-29 (colon carcinoma), HTB-54 (lung carcinoma), PC-3 (prostate carcinoma), MCF-7 (breast adenocarcinoma), 184B5 (non-malignant, mammary gland derived) and BEAS-2B (non-malignant, derived from bronchial epithelium). Most of the compounds displayed high antiproliferative activity with GI50 values below 10 μM in MCF-7, CCRF-CEM and PC-3 cells. Radical scavenging properties of the new selenocompounds were confirmed testing their ability to scavenge DPPH and ABTS radicals. Based on the activity of selenium-based glutathione peroxidases (GPxs), compounds 1a, 2e and 2h were further screened for their capacity to reduce hydrogen peroxide under thiol presence. Results suggest that compound 1a mimics GPxs activity. Cytotoxic parameters, radical scavenging activity and ADME profile point to 1a as promising drug candidate.
- Romano, Beatriz,Plano, Daniel,Encío, Ignacio,Palop, Juan Antonio,Sanmartín, Carmen
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p. 1716 - 1727
(2015/03/30)
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- Synthesis and antiproliferative activity of novel methylselenocarbamates
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A series of new aliphatic, aromatic and heteroaromatic carbamate derivatives containing a methylseleno moiety were synthesized and evaluated in vitro for their cytotoxic activity against a panel of human cell lines including CCRF-CEM (lymphoblastic leukaemia), K-562 (lymphocytic leukaemia), HT-29 (colon carcinoma), HTB-54 (lung carcinoma), PC-3 (prostate carcinoma), MCF-7 (breast adenocarcinoma), 184B5 (non-malignant, mammary gland derived) and BEAS-2B (non-malignant, derived from bronchial epithelium). Most of the compounds are highly cytotoxic with GI50 values below 10 μM in every tested tumour cell line. Based on its cytotoxic parameters, selectivity index and ADME profile, the biological activity of compound 2, the propyl derivative, was further analysed in CCRF-CEM and HTB-54 cells. Results showed that this compound is able to induce apoptosis in a time- and dose-dependent manner. Involvement of caspases in cell death induction by 2 was detected. Besides, compound 2 was also able to induce cell cycle arrest at G0/G1 in CCRF-CEM cells and at G2/M in HTB-54 cells.
- Romano, Beatriz,Font, María,Encío, Ignacio,Palop, Juan Antonio,Sanmartín, Carmen
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p. 674 - 684
(2014/07/22)
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- β-type glycosidic bond formation by palladium-catalyzed decarboxylative allylation
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The efficient and stereoselective construction of glycosidic linkages is of great significance in carbohydrate chemistry due to the ubiquitous existence of numerous biologically active natural products and saccharides. Although great efforts have been devoted to stereoselective glycosylations in the past few decades, constructing glycosidic bonds with high efficiency and selectivity remains a challenge and continues to be an important area in carbohydrate research. Phenols are widely used as nucleophiles in palladium-catalyzed allylation. In contrast, the possibility of using aliphatic alcohols as nucleophiles is not as thoroughly explored. The modified reaction conditions were then applied to other substrates. Originating from easily prepared carbonates, various glycosides, such as phenolic Oglycosides, thiophenolic S-glycoside, aliphatic O-glycosides, and even disaccharides, were synthesized in good yields by means of a palladium-catalyzed decarboxylative allylation.
- Xiang, Shaohua,Lu, Zhiqiang,He, Jingxi,Hoang, Kim Le Mai,Zeng, Jing,Liu, Xue-Wei
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supporting information
p. 14047 - 14051
(2013/11/19)
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- 1-(Hydroxyacetyl)pyrene a new fluorescent phototrigger for cell imaging and caging of alcohols, phenol and adenosine
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1-(Hydroxyacetyl)pyrene has been introduced as a new fluorescent phototrigger for alcohols and phenols. Alcohols and phenols were protected as their corresponding carbonate esters by coupling with fluorescent phototrigger, 1-(hydroxyacetyl)pyrene. Photophysical studies of caged carbonates showed that they all exhibited strong fluorescence properties. Irradiation of the caged carbonates by visible light (≥410 nm) in aqueous acetonitrile released the corresponding alcohols or phenols in high chemical (95-97%) and quantum (0.17-0.21) yields. The mechanism for the photorelease was proposed based on Stern-Volmer quenching experiments and solvent effect studies. Importantly, 1-(hydroxyacetyl)pyrene showed as a phototrigger for rapid photorelease of the biologically active molecule adenosine. In vitro biological studies revealed that 1-(hydroxyacetyl)pyrene has good biocompatibility, cellular uptake property and cell imaging ability. The Royal Society of Chemistry and Owner Societies 2012.
- Jana, Avijit,Saha, Biswajit,Ikbal, Mohammed,Ghosh, Sudip Kumar,Singh, N. D. Pradeep
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p. 1558 - 1566
(2013/02/26)
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- Synthesis, insecticidal evaluation of novel 1,3,4-thiadiazole chrysanthemamide derivatives formed by an EDCI/HOBt condensation
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A series of novel pesticides with two components derived from a 1,3,4-thiadiazole and chrysanthemic acid were synthesised via an EDCI/HOBt condensation. These 1,3,4-thiadiazole chrysanthemamides were identified by IR, 1H NMR and elemental analyses. Their insecticidal activity was also evaluated.
- Yu, Peng,Hu, Jun,Zhou, Tao-Yu,Wang, Peng,Xu, Yan-Hua
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experimental part
p. 703 - 706
(2012/03/10)
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- (Cyclopentadienyl)ruthenium-catalyzed regio- and enantioselective decarboxylative allylic etherification of allyl aryl and alkyl carbonates
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(Cyclopentadienyl)tris(acetonitrile)ruthenium hexafluorophosphate {[CpRu(NCMe)3][PF6] or (cyclopentadienyl) (I·6-naphthalene)ruthenium hexafluorophosphate {[CpRu(I·6-naphthalene)][PF6]} in combination with a pyridine oxazoline ligand efficiently catalyze the decarboxylative allylic rearrangement of allyl aryl carbonates. Good levels of regio- and enantioselectivity are obtained. Starting from enantioenriched secondary carbonates, the reaction is stereospecific and the corresponding allylic ethers are obtained with net retention of configuration. An intermolecular version of this transformation was also developed using allyl alkyl carbonates as substrates. Conditions were found to obtain the corresponding products with similar selectivity as in the intramolecular process. Through the use of a hemi-labile hexacoordinated phosphate counterion, a zwitterionic air- and moisture-stable chiral ruthenium complex was synthesized and used in the enantioselective etherification reactions. This highly lipophilic metal complex can be recovered and efficiently reused in subsequent catalysis runs. Copyright
- Austeri, Martina,Linder, David,Lacour, Jerome
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experimental part
p. 3339 - 3347
(2011/02/23)
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- NOVEL VINBLASTINE DERIVATIVES, THEIR PREPARATION, USE AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAID DERIVATIVES
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The invention provides vinblastine derivatives represented by the following formula 1 or their physiologically acceptable salts, their preparation, use and pharmaceutical compositions comprising the said derivatives. The said vinblastine derivatives show inhibiting activities against tumor cell lines and can be used as medicaments for treating malignant tumors.
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Page/Page column 43
(2009/12/05)
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- Thioether substituted aryl carbonate protecting groups
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Embodiments of the invention include thioether substituted aryl carbonate protecting groups, and nucleoside monomers protected with thioether substituted aryl carbonate protecting groups. Aspects of the invention further included methods of synthesizing nucleic acids, e.g., oligonucleotides, using such protected nucleoside monomer monomers, as well as nucleic acids produced using methods of the invention and compositions thereof.
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- ORGANIC COMPOUNDS
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The present invention provides heterocyclic derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.
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Page/Page column 99-100
(2008/12/08)
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- Process for preparing alkyl/aryl chloroformates
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The present invention discloses an improved method for the preparation of alky/aryl chloroformates directly from alcohols and triphosgene. This method is simple, mild and efficient avoids use of hazardous phosgene. It can be used for the preparation of various aryl as well as alkyl chloroformates in excellent yields.
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Page/Page column 2
(2010/02/11)
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- Preparation of chloroformates using bis(trichloromethyl)carbonate
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The synthesis of eight chloroformates using bis(trichloromethyl) carbonate(BTC) is reported. It has been found that the yields by this BTC method are improved over the earlier phosgene method, and sodium hydroxide is better than pyridine as catalyst for the preparation of phenyl chloroformate.
- Shi, Haibo,Hu, Weixiao,Sun, Yaquan
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p. 708 - 709
(2007/10/03)
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- Therapeutic compounds
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The present invention provides compounds, for example, of formula (I): wherein R1, R2, and R3 have any of the values defined in the specification, as well as pharmaceutical compositions comprising the compounds. The invention also provides therapeutic methods, and processes and intermediates useful for preparing compounds of formula I.
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- Benzyl chloroformate (CbzCl) synthesis using carbon monoxide as a carbonyl source
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A novel non-phosgene synthetic method for benzyl chloroformate (CbzCl) was established. S-Methyl O-benzyl carbonothioates were prepared by the carbonylation of benzyl alcohols with carbon monoxide and sulfur (or carbonyl sulfide) in the presence of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) followed by esterification using methyl iodide in good yields. Then, CbzCl derivatives were successfully synthesized by the chlorination of S-methyl O-benzyl carbonothioates using sulfuryl chloride in excellent yields.
- Mizuno, Takumi,Takahashi, Junko,Ogawa, Akiya
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p. 10011 - 10015
(2007/10/03)
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- A facile synthesis of azidoformate via chloroformate
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This work synthesized chloroformates by slowly adding alcohols into a suspension of trichloromethyl chloroformate, instead of phosgene, along with activated charcoal in tetrahydrofuran. This chloroformylation yielded chloroformates in near quantitative yield. The subsequent reaction between chloroformates and sodium azide in dry acetone produced azidoformates in a high yield.
- Wu, Pei-Lin,Su, Chia-Hao,Gu, Yi-Jeng
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p. 271 - 274
(2007/10/03)
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- Catalyst for decarbonylation reaction
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A catalyst composed of an organic phosphorus compound having a trivalent or pentavalent phosphorus atom and at least one carbon-phosphorus bonding or a combination of the organic phosphorus compound and a halogen atom-containing compound is effective for decarbonylation, that is, for releasing carbon monoxide from a compound containing a moiety of --CO--CO--O-- in its molecular structure.
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- Catalyst for decarbonylation reaction
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A catalyst composed of an organic phosphorus compound having a trivalent or pentavalent phosphorus atom and at least one carbon-phosphorus bonding or a combination of the organic phosphorus compound and a halogen atom-containing compound is effective for decarbonylation, that is, for releasing carbon monoxide from a compound containing a moiety of -CO-CO-O- in its molecular structure.
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- Inhibitors of farnesyl protein transferase. 4-Amido, 4-carbamoyl, and 4- carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]- cyclohepta[1,2-b]pyridin-11-yl)piperazine and 1-(3-bromo-8-chloro-6,11- dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazine
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The synthesis of a variety of novel 4-amido, 4-carbamoyl and 4- carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H- benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazine to explore the SAR of of this series of FPT inhibitors is described. This resulted in the synthesis of the 4-and 3-pyridylacetyl analogues 45a and 50a, respectively, both of which were orally active but were found to be rapidly metabolized in vivo. Identification of the principal metabolites led to the synthesis of a variety of new compounds that would be less readily metabolized, the most interesting of which were the 3- and 4-pyridylacetyl N-oxides 80a and 83a. Novel replacements for the pyridylacetyl moiety were also sought, and this resulted in the discovery of the 4-N-methyl and 4-N-carboxamidopiperidinylacetyl derivatives 135a and 160a, respectively. All of these derivatives exhibited greatly improved pharmacokinetics. The synthesis of the corresponding 3- bromo analogues resulted in the discovery of the 4-pyridylacetyl N-oxides 83b (±) and 85b [11S(-)] and the 4-carboxamidopiperidinylacetamido derivative 160b (±), all of which exhibited potent FPT inhibition in vitro. All three showed excellent oral bioavailability in vivo in nude mice and cynomolgus monkeys and exhibited excellent antitumor efficacy against a series of tumor cell lines when dosed orally in nude mice.
- Mallams, Alan K.,Rossman, Randall R.,Doll, Ronald J.,Girijavallabhan, Viyyoor M.,Ganguly, Ashit K.,Petrin, Joanne,Wang, Lynn,Patton, Robert,Bishop, W. Robert,Carr, Donna M.,Kirschmeier, Paul,Catino, Joseph J.,Bryant, Matthew S.,Chen, Kwang-Jong,Korfmacher, Walter A.,Nardo, Cymbelene,Wang, Shiyong,Nomeir, Amin A.,Lin, Chin-Chung,Li, Zujun,Chen, Jianping,Lee, Suining,Dell, Janet,Lipari, Philip,Malkowski, Michael,Yaremko, Bodan,King, Ivan,Liu, Ming
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p. 877 - 893
(2007/10/03)
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- Hapten Synthesis and Production of Monoclonal Antibodies to the N-Methylcarbamate Pesticide Methiocarb
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With the aim of developing an immunoassay for the detection of the insecticide methiocarb, three compounds with carboxylic spacer arms of different lengths introduced at the carbamate group were synthesized, conjugated to proteins, and used as immunizing haptens in mice. Monoclonal antibodies (MAbs) were subsequently obtained and characterized for their affinity to methiocarb. In the homologous conjugate-coated assay format, MAbs exhibited I5o values in the 1 -10 nM range. Thereafter, a collection of methiocarb haptens with modifications in the aromatic ring structure or in the spacer arm were synthesized to be used as heterologous haptens. These haptens and MAbs were incorporated into several ELISA configurations. Some of the new combinations of immunoreagents and assay format provided a significant improvement in assay sensitivity, reaching I50 values around 0.1 nM. MAbs seem to be very specific for methiocarb, as evidenced by the negligible cross-reactivity shown by methiocarb metabolites. These immunoreagents are very promising analytical tools for the rapid and sensitive determination of methiocarb in food and in the environment.
- Abad, Antonio,Moreno, María José,Montoya, Angel
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p. 2417 - 2426
(2007/10/03)
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- Preparation of aryl chloroformates
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A process for preparing an aryl chloroformate is disclosed that involves the reaction of a phenol with phosgene in the presence of a cyclic urea.
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- Process for the preparation of aryl carbonates
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Carbonates with aromatic ester groups are prepared by reaction of aromatic monohydroxy compounds with phosgene or with chloroformic acid esters of aromatic monohydroxy compounds, whereby operations are carried out at a temperature in the range of 50° to 450° C. and at a pressure in the range of 0.05 to 20 bar in the presence of metallates of the elements of groups IIIa, IVa, Va, VIa, IIIb, IVb, Vb, VIb, VIIb, and VIII of the Mendeleev periodic system as heterogeneous catalysts.
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- Process for the production of aryl carbonates
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Carbonates with aromatic ester groups may be produced by reacting aromatic monohydroxy compounds with phosgene or with chlorocarbonates of aromatic monohydroxy compounds, wherein a temperature in the range from 50° to 450° C. and a pressure in the range from 0.05 to 20 bar are used in the presence of hard materials with metal-like properties (ceramic precursors) as heterogeneous catalysts.
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- Process for the preparation of aryl haloformates and diaryl carbonates
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A process of preparing diaryl carbonates, such as diphenyl carbonate, and aryl haloformates, such as phenyl chloroformate. The process involves contacting phenol or a substituted phenol with a carbonyl halide, such as phosgene, in the presence of a phosphorus-containing catalyst. The catalyst is selected from alkyl phosphates, aryl phosphites, aryl phosphates, organic phosphinites and phosphinates, organic pyrophosphates, inorganic phosphorous and phosphoric acids, and phosphorus oxides.
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- Heat-sensitive recording materials and phenol compounds
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Heat-sensitive recording materials contain an electron-donating chromogenic compound and an electron-attracting compound. The recording materials also contain at least one compound represented by the following formula: STR1 wherein R1 and R3 mean a hydrogen atom or an alkyl, aralkyl or aryl group, R2 and R4 denote an alkyl, alkenyl, aralkyl or aryl group, X1, X2, Y1 and Y2 stand for an oxygen or a sulfur atom, and --Z1 -- and --Z2 -- are a specific aromatic group. Also provided are phenol compounds represented by the following formula: STR2 wherein R1, R2, X1 and Y1 have the same meanings as defined above; R5 and R6 are a hydrogen or halogen atom or an alkyl, alkoxy, aralkyl, aryl or hydroxyl group; p and q stand for an integer of 1-4; R5 and R6 may be either the same or different when p and q represent an integer of 2 or greater; and --Z3 -- means a specific divalent group.
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- Process for preparting aryl carbonates
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Carbonates with aromatic ester groups may be prepared by reacting aromatic monohydroxy compounds with phosgene or with chloroformates of aromatic monohydroxy compounds, wherein the process is performed at a temperature in the range 50°-350° C. in the presence of aluminosilicates as heterogeneous catalysts.
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- Pyridinium derivatives, their production and use
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Novel pyridinium derivatives represented by the formula (I): STR1 wherein STR2 is an optionally substituted pyridinium ring; R1 is a lower alkyl group or aralkyl group; R7 and R10 are independently hydrogen, a lower alkyl group, aryl group or aralkyl group; l is 0 or 1; R5 is a phenylene group or an alkylene group which may be substituted; R11 is an alkyl group or aryl group; X is a group of the formula: --CH2 OCH2 -- or a group of the formula: STR3 wherein R6 is hydrogen, a lower alkyl or a lower alkoxy, and m is an integer of 0 to 3; U is a group of the formula: STR4 wherein R4 is hydrogen, a lower alkyl group, aryl group or aralkyl group; Y and Z are independently a divalent chain group consisting of one to six members which is selected from the class consisting of groups of the formulae: STR5 wherein R is hydrogen, a lower alkyl group, acyl group or aryl group and at least one of which is a group of the formula: STR6 with the proviso that R may be the same or different from each other, or may form a ring together when two or more groups of the formula: STR7 are present, that R may be bonded to R4 when Y contains a group of the formula: STR8 and that R may be bonded to R11 when Z contains a group of the formula: STR9 and W? is a counter anion; are useful as a platelet activating factor antagonist.
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- Water-soluble, monoazo dyes containing a ureido group and two sulfonyl fiber-reactive groups
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This invention is directed to new water-soluble, monoazo dyes having the following general formula: STR1 in which: X and Y are independently selected from the group consisting of: STR2 R, R1, R2 are independently selected from H, lower alkyl of one to four carbons and sulfonated lower alkyl; A is a phenyl or napthyl radical optionally substituted with halogen, hydroxy, lower alkyl, lower alkoxy, carboxylic acid or sulfonic acid; W is a phenyl or naphthyl radical optionally substituted by carboxylic acid, sulfonic acid, amino, amido, lower alkyl, lower alkoxy, hydroxy or halogen groups; Z is a phenyl radical optionally substituted with halogen, lower alkoxy or lower alkyl groups; and copper, chromium, cobalt and nickel metallized complexes of said dyestuffs. The dyes of this invention on cellulose textiles have high tinctorial strength, purity of shade, light and wash fastness particularly chlorine wash fastness. They are particularly useful in high temperature dyeing operations and can be prepared into stable aqueous solutions for use in continuous dyeing operations. The dyes of this invention provide a full range of shades and exhibit superior color yield and leveling in chemical pad steaming dyeing. They build strongly with superior fixation and have superior stability in acidic and alkaline environments.
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- Acid halides, a process for their preparation
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An N-alkylated formamide of the formula STR1 wherein R1 denotes alkyl R2 denotes alkyl with at least 9 carbon atoms or the group STR2 wherein A denotes straight-chain or branched alkanediyl, R1 denotes lower alkyl and n denotes an integer from 2 to 6, a process for the preparation of the same and its use in the replacement of a hydroxyl group in an organic compound by chlorine or bromine the improvement wherein the replacement is carried out in the presence of an N-alkylated formamide.
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- Chemiluminescence from arylcarbene oxidation: phenylchlorocarbene and (2-chlorophenyl)carbene
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Chemiluminescence is observed in the thermal reaction of phenylchlorocarbene or (2-chloro-phenyl)carbene and O2, matrix-isolated in Ar.The chemiluminescence spectra closely match the phosphorescence of the corresponding carbonyl compounds.The reactivity of both carbenes towards O2 is very different.Singlet carbene phenylchlorocarbene reacts thermally only slowly with O2 up to 60 K.The oxidation products phenylchloroformate, benzoyl chloride and O(3P) are mainly formed photochemically on irradiation of the diazirine precursor.Triplet carbene (2-chlorophenyl)carbene reacts readily with O2 at cryogenic temperatures to give mostly 2-chlorobenzaldehyde-O-oxide.The carbonyl-O-oxide is photochemically easily cleaved to give 2-chlorobenzaldehyde and O(3P).The reaction step leading to carbonyl compounds in their excited states is in both carbene oxidations the recombination of the free carbene and O(3P).
- Sander, Wolfram W.
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p. 637 - 646
(2007/10/02)
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- Reaction of Phenylchlorocarbene in Oxygen-Doped Matrices
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Irradiation of phenylchlorodiazirine at 10 K matrix isolated in argon gives phenylchlorocarbene.The carbene was characterized by IR, UV, and trapping with HCl.Warming an argon matrix containing O2 and the carbene to 35 K caused reaction to give the corresponding carbonyl oxide.The yellow-green (λmax 400nm) carbonyl oxide was characterized by IR, Uv, and 18O2 labeling.Photolysis of the carbonyl oxide with visible light gave the corresponding dioxirane, benzoyl chloride, and ozone.The dioxirane, which showed only absorption tailing into the visible, was characterized by IR, 18O2 labeling, and subsequent photochemistry.Irradiation of the dioxirane (λ>/=420 nm) gave mainly phenyl chloroformate and a small amount of chlorobenzene and CO2.Possible mechanism for the novel spin-forbidden O2 addition are discussed.
- Ganzer, Georg A.,Sheridan, Robert S.,Liu, Michael T. H.
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p. 1517 - 1520
(2007/10/02)
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- Acylation du trifluoromethoxybenzene en catalyse HF-BF3
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Friedel and Crafts acylation of trifluoromethoxy- and trifluoromethyl-thiobenzene fails to give ketones in a one step synthesis if chlorinated Lewis acids (AlCl3) are used, because of halogen exchange on the -OCF3 and -SCF3 groups.The use of a fluorinated catalyst system such as HF-BF3 avoids exchange reactions and acylation occurs smoothly under mild conditions: - Low temperature and pressure - High yields (very often >90 percent) - Very high para-regioselectivity.Related reactions such as formylation or sulfonylation can also be achieved under similar conditions.
- Desbois, Michel
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p. 885 - 890
(2007/10/02)
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- Synthesis an CuCN-Promoted Cyanation of Iodoformic Esters
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A number of iodoformic esters have been prepared, isolated, and identified for the first time.Phenyl iodoformate has been converted into phenyl cyanoformate under mild conditions.Decarboxylative iodination of iodoformates ROCOIto give RI and CO2 can be slowed down by the choice of the group R.
- Hoffmann, H.M.R.,Iranshahi, Lotfollah
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p. 1174 - 1176
(2007/10/02)
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- Nuclear Magnetic Resonance Studies of Iminium Salts. Part 11. Anionic Paticipation of Iminium Salts in Phosgenation Reactions
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Iminium salts act as catalysts in the reaction of phosgene and phenols or thiols to yield chloroformates, which are important synthetic intermediates.This effect is explained in terms of the nucleophilicity of the chloride anion of the salts on the basis of an n.m.r. identification of various intermediates.The mechanism of nucleophilic assistance of iminium salts towards the substrate can be understood as an increase of the nucleophilicity of phenol or thiol by proton abstraction from the OH or SH group by the chloride anion.
- Gauvreau, Jean R.,Martin, Gerard J.,Malfroot, Thierry,Senet, Jean Pierre
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p. 1971 - 1974
(2007/10/02)
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- Process for the preparation of chloroformic acid aryl esters
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In a process for the preparation of an aromatic chloroformic acid ester by contacting a phenol and phosgene, the improvement wherein the reaction is carried out in a homogeneous liquid phase at a temperature of 60° to 180° C. in the presence of organic phosphorus compound of the formula in which R1, R2 and R3 independently of one another represent hydrogen, alkyl, alkenyl, aralkyl, aryl or halogen and two of the said radicals together with the phosphorus atom can form a 5-membered or 6-membered phosphorus-containing saturated or unsaturated heterocyclic radical, X represents OH, homopolar-bonded halogen or an inorganic or organic acid anion, R4 denotes hydrogen or alkyl or, if X denotes halogen, can also denote halogen and n denotes 0 or 1, and in which, furthermore, R4 and X together can represent oxygen or sulfur.
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- Carbamates
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Carbamate compounds of the formula: in which CO.X.CO is the diacyl radical of a polybasic carboxylic acid, and R1 is an optionally substituted hydrocarbyl radical; more particularly, X is a member of the group consisting of a direct link, C1 to C4 alkylene groups, C2 to C3 alkenylene, o-phenylene and p-phenylene and R1 is a member of the group consisting of C1 to C18 alkyl, phenyl, chlorophenyl, nitrophenyl, cyclohexyl and benzyl. These carbamates are useful as cross-linking agents in natural rubbers or synthetic rubbers based on isoprene or butadiene polymers.
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- Process for the preparation of chloroformic acid aryl esters and cyclic carbonates
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A process for the preparation of chloroformic acid aryl-esters and cyclic carbonates of aryl compounds containing at least two phenolic hydroxy groups wherein aromatic compounds containing one or more hydroxy groups linked to an aromatic nucleus, are reacted with phosgene in the presence of catalytic amounts of N,N-disubstituted acid amide either under pressure or without pressure while removing the hydrogen chloride continuously from the reaction mixture. This improved process results in almost quantitative or very high yields of pure products and avoids problems such as disposal of waste water.
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- Process for preparing alkyl isocyanates
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Alkylisocyanates are prepared by reacting a phenol or substituted phenol and phosgene in a halogenated hydrocarbon solvent with aqueous alkali metal hydroxide to produce a corresponding chloroformate, reacting the resulting chloroformate solution with aqueous alkylamine to give a corresponding N-alkylcarbamate which, after solvent is stripped, is then pyrolyzed to yield the alkyl isocyanate. Solvent and the starting phenol may be recovered and recycled to the process.
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